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Background: The "Iron Swords" War beginning in October 2023 led to unprecedented levels of shock and trauma across Israel, significantly impacting the Israeli population and medical personnel. This study aimed to evaluate and compare the perceived personal resilience and sense of danger among physicians in hospitals located in different conflict zone proximities in Israel during this period. Methods: A quantitative, cross-sectional study was conducted from March to August 2024, during an active phase of the war, using a structured anonymous questionnaire. Participants were 161 physicians from three hospitals: one in southern Israel near the Gaza Strip, another in northern Israel near the borders with Lebanon, Syria, and Jordan, and a third in central Israel near Tel Aviv. The survey measured personal resilience using the Connor-Davidson Resilience Scale (CD-RISC-10) and sense of danger using the Solomon & Prager scale. Statistical analyses included Kruskal-Wallis H test, multiple linear regression, two-way analysis of variance (ANOVA), and Sobel test for mediation effects. Results: The final sample included 161 physicians (54 southern, 56 central, 51 northern). The mean resilience score was 31.14 ± 5.77, and the mean sense of danger score was 8.36 ± 4.15 (scales 0–40 and 0–20, respectively). Physicians in the southern hospital reported significantly higher sense of danger scores (p = 0.005). A trend towards lower resilience scores was noted among southern hospital physicians (p = 0.068) (p = 0.068). Two-way ANOVA revealed significant main effects of hospital location and gender on resilience (p = 0.046 and p = 0.003, respectively) and sense of danger (p = 0.005 and p = 0.062, respectively). Multiple regression analysis identified hospital location (β = -0.178, p = 0.023) and gender (β = 0.229, p = 0.004) as significant predictors of resilience. Mediation analysis indicated that personal resilience partially mediated the relationship between hospital location and sense of danger (indirect effect = 0.2896, p < 0.001). Conclusions: Physicians working near conflict zones report higher levels of perceived danger, though their resilience is comparable to peers in less threatened regions. Enhancing personal resilience is crucial to mitigate the heightened sense of danger. This could include regular resilience training, psychological support, and specific programs for single and childless physicians to improve safety perceptions. Additionally, fostering a supportive community with clear communication and robust emergency protocols is essential for enhancing staff resilience and safety in hospitals. [ABSTRACT FROM AUTHOR]

Background: Depression acts as a noteworthy worldwide public health challenge. Identifying accessible biomarkers is crucial for early diagnosis and intervention. The relationship between depression in adult Americans and the neutrophil to high-density lipoprotein cholesterol ratio (NHR) was investigated in this research. Methods: The relationship between NHR and depressive symptoms was analyzed utilizing National Health and Nutrition Examination Survey data from 2005 to 2018 and the Patient Health Questionnaire-9. The study included 33,871 participants with complete NHR and depression data. Adjusted multivariable logistic regression models were used to account for possible confounders, and subgroup analyses were conducted to investigate effect changes. Results: Elevated NHR levels were positively correlated with a heightened risk of depression (OR = 1.03, 95% CI: 1.01–1.05, P < 0.0005). After the NHR was divided into tertiles, those in the top tertile had an 18% higher chance of developing depression than those in the bottom tertile (OR = 1.18; 95% CI: 1.05–1.32; P for trend = 0.0041). Subgroup analyses revealed variations in this association based on race and marital status. Additionally, the relationship between NHR and depression demonstrated a U-shaped pattern, with a significant breakpoint identified at an NHR of 6.97. Conclusion: These results imply that the NHR may be a potential biomarker for depression risk, with implications for early detection and personalized treatment. Further research is needed to elucidate the mechanisms underlying the NHR-depression link and establish causality. [ABSTRACT FROM AUTHOR]

Background: Both genetic and environmental factors play crucial roles in the development of major depressive disorder (MDD) and suicide attempts (SA). However, the interaction between both items remains unknown. This study aims to explore the interactions between the genetic variants of the serotonin 2 A receptor (HTR2A) and the nitric oxide synthase 1 (NOS1) and environmental factors in patients who experience MDD and SA. Methods: A total of 334 patients with MDD and a history of SA (MDD-SA) were recruited alongside 518 patients with MDD with no history of SA (MDD-NSA), and 716 healthy controls (HC). The demographic data and clinical characteristics were collected. Sequenom mass spectrometry was used to detect eight tag-single nucleotide polymorphisms (tagSNPs) in HTR2A (rs1328683, rs17068986, and rs3125) and NOS1 (rs1123425, rs2682826, rs3741476, rs527590, and rs7959232). Generalized multifactor dimensionality reduction (GMDR) was used to analyze the gene-environment interactions. Results: Four tagSNPs (rs17068986, rs3125, rs527590, and rs7959232) exhibited significant differences between the three groups. However, these differences were not significant between the MDD-SA and MDD-NSA groups after Bonferroni correction. A logistic regression analysis revealed that negative life events (OR = 1.495, 95%CI: 1.071–2.087, P = 0.018), self-guilt (OR = 2.263, 95%CI: 1.515–3.379, P < 0.001), and negative cognition (OR = 2.252, 95%CI: 1.264–4.013, P = 0.006) were all independently associated with SA in patients with MDD. Furthermore, GMDR analysis indicated a significant interaction between HTR2A rs3125 and negative life events. Negative life events in conjunction with the HTR2A rs3125 CG + GG genotype were associated with a higher SA risk in patients with MDD when compared to the absence of negative life events in conjunction with the CC genotype (OR = 2.547, 95% CI: 1.264–5.131, P = 0.009). Conclusion: Several risk factors and a potential interaction between HTR2A rs3125 and negative life events were identified in patients with SA and MDD. The observed interaction likely modulates the risk of MDD and SA, shedding light on the pathogenesis of SA in patients with MDD. [ABSTRACT FROM AUTHOR]

Background: Following exposure to traumatic stress, women are twice as likely as men to develop mood disorders. Yet, individual responses to such stress vary, with some people developing stress-induced psychopathologies while others exhibit resilience. The factors influencing sex-related disparities in affective disorders as well as variations in resilience remain unclear; however, emerging evidence suggests differences in the gut microbiota play a role. In this study, using the single prolonged stress (SPS) model of post-traumatic stress disorder, we investigated pre- and post-existing differences in microbial composition, functionality, and metabolites that affect stress susceptibility or resilience in each sex. Methods: Male and female Sprague–Dawley rats were randomly assigned to control or SPS groups. Two weeks following SPS, the animals were exposed to a battery of behavioral tests and decapitated a day later. Based on their anxiety index, they were further categorized as SPS-resilient (SPS-R) or SPS-susceptible (SPS-S). On the day of dissection, cecum, and selected brain tissues were isolated. Stool samples were collected before and after SPS, whereas urine samples were taken before and 30 min into the SPS. Results: Before SPS exposure, the sympathoadrenal axis exhibited alterations within male subgroups only. Expression of tight junction protein claudin-5 was lower in brain of SPS-S males, but higher in SPS-R females following SPS. Across the study, alpha diversity remained consistently lower in males compared to females. Beta diversity revealed distinct separations between male and female susceptible groups before SPS, with this separation becoming evident in the resilient groups following SPS. At the genus level, Lactobacillus, Lachnospiraceae_Incertae_Sedis, and Barnesiella exhibited sex-specific alterations, displaying opposing abundances in each sex. Additionally, sex-specific changes were observed in microbial predictive functionality and targeted functional modules both before and after SPS. Alterations in the microbial short-chain fatty acids (SCFAs), were also observed, with major and minor SCFAs being lower in SPS-susceptible males whereas branched-chain SCFAs being higher in SPS-susceptible females. Conclusion: This study highlights distinct pre- and post-trauma differences in microbial composition, functionality, and metabolites, associated with stress resilience in male and female rats. The findings underscore the importance of developing sex-specific therapeutic strategies to effectively address stress-related disorders. Highlights SPS model induces divergent anxiety and social behavioral responses to traumatic stress in both male and female rodents. SPS-resilient females displayed less anxiety-like behavior and initiated more interactions towards a juvenile rat than SPS-resilient males. Sex-specific pre-existing and SPS-induced differences in the gut microbial composition and predictive functionality were observed in susceptible and resilient rats. SPS-resilient males displayed elevated cecal acetate levels, whereas SPS-susceptible females exhibited heightened branched-chain SCFAs. Plain language summary: After experiencing traumatic stress, women are more likely than men to develop mood disorders like anxiety and depression. However, people's responses to trauma vary—some develop mental health issues while others remain resilient. Recent research suggests that the bacteria in the gut might play a role in these differences. In this study, using a rat model of post-traumatic stress disorder (PTSD), we investigated whether there are differences in gut bacteria between male and female rats before and after stress exposure. The study involved two groups of rats—one not exposed to stress (control) and the other exposed to a traumatic event (stressed). The rats' behavior was evaluated using different tests to determine who among the males and females were vulnerable to stress and who were resilient. We found that even before the stress, there were differences in the types of bacteria and their functions in the guts of male and female rats. These differences were also linked to how they responded to stress. Interestingly, the bacteria that were more abundant in resilient males were found to be more abundant in vulnerable females. Additionally, the traumatic stress affected these bacteria and the substances they produce differently in males and females. In essence, our study demonstrates that the types of gut bacteria, their functions, and their products contribute to stress resilience in different ways for male and female rats. This insight suggests that tailored treatments specifically targeting these differences could be specially effective in treating stress-related issues. [ABSTRACT FROM AUTHOR]

Background: Premenstrual Syndrome (PMS) is a common public health issue affecting many women of reproductive age worldwide. This study has been designed to investigate of computer-based stress inoculation training (SIT) counseling approach on anxiety, depression, and stress of university students with PMS. Methods: A randomized trial study with two parallel arms was done from 30 October 2022 to 21 June 2023 on 100 university students aged 18 to 38 at Babol University of Medical Sciences. The participants were randomly divided into two groups intervention and control. The data collection tools included questionnaires on demographic-fertility characteristics, the Premenstrual Symptoms Screening Tool (PSST), the Hospital Anxiety and Depression Scale (HADS), the Perceived Stress Scale (PSS-14), the Sheehan Disability Scale (SDS) and Riff’s Psychological Well-being Scale (RPWS). The data were assessed using chi-square, t-student, ANOVA repeated measure, and linear regression tests. A significance level of P < 0.05 was considered for the analysis. Results: The results of the study showed that the SIT interventions decreased the PMS severity and most psychological factors so in the intervention group, SIT was able to significantly reduce anxiety, depression, perceived stress, and Sheehan’s disability after intervention (P < 0.001). Based on multiple linear regression analysis, the most predictors of HADS were the PSS and SDS (β = 0.285, p = 0.009 and β = 0.236, p = 0.024, respectively). Conclusion: The computer-based SIT counseling approach could reduce the severity of symptoms and psychological factors in students. Therefore, SIT intervention is recommended to manage their PMS. Trial registration: IRCT20230130057274N2. [ABSTRACT FROM AUTHOR]

Background: Patients with musculoskeletal disorders (MSDs) access health care in different ways. Despite the high prevalence and significant costs, we know little about the different ways patients use health care. We aim to fill this gap by identifying which combinations of health care services patients use for new MSDs, and its relation to clinical characteristics, demographic and socioeconomic factors, long-term use and costs, and discuss what the implications of this variation are. Methods: The study combines Norwegian registers on health care use, diagnoses, comorbidities, demographic and socioeconomic factors. Patients (≥ 18 years) are included by their first health consultation for MSD in 2013–2015. Latent class analysis (LCA) with count data of first year consultations for General Practitioners (GPs), hospital consultants, physiotherapists and chiropractors are used to identify combinations of health care use. Long-term high-cost patients are defined as total cost year 1–5 above 95th percentile (≥ 3 744€). Results: We identified seven latent classes: 1: GP, low use; 2: GP, high use; 3: GP and hospital; 4: GP and physiotherapy, low use; 5: GP, hospital and physiotherapy, high use; 6: Chiropractor, low use; 7: GP and chiropractor, high use. Median first year health care contacts varied between classes from 1–30 and costs from 20€-838€. Eighty-seven percent belonged to class 1, 4 or 6, characterised by few consultations and treatment in primary care. Classes with high first year use were characterised by higher age, lower education and more comorbidities and were overrepresented among the long-term high-cost users. Conclusion: There was a large variation in first year health care service use, and we identified seven latent classes based on frequency of consultations. A small proportion of patients accounted for a high proportion of total resource use. This can indicate the potential for more efficient resource use. However, the effect of demographic and socioeconomic variables for determining combinations of service use can be interpreted as the health care system transforming unobserved patient needs into variations in use. These findings contribute to the understanding of clinical pathways and can help in the planning of future care, reduction in disparities and improvement in health outcomes for patients with MSDs. [ABSTRACT FROM AUTHOR]

Background: Fibromyalgia (FM) is a chronic condition characterized by widespread musculoskeletal pain, fatigue, intestinal disorders, mood swings, and sleep disturbances. To the best of our knowledge, the questionnaire used for assessing problems and difficulties in the functioning of people with FM has not been translated and adapted in Poland so far. The aim of the study was to assess the psychometric properties of the Polish version of the Fibromyalgia Impact Questionnaire (FIQ-Pol). Material and method: The study covered 150 people with FM living in Poland. The measurement reliability, internal structure, repeatability, and validity of the Polish version of the FIQ were examined. Results: The scale score reliability of the entire tool for the research group was very good. The alpha Cronbach's test result for the whole scale was 0.84. The repeatability of the scale measured by the test–retest method using the interclass correlation coefficients (ICC) was very good and amounted to 0.96. Internal structure suggested by FIQ-Pol authors was confirmed (Confirmatory factor analysis). After introducing modification indices for the entire scale, satisfactory parameter values were obtained, i.e.: RMSEA (0.06), CFI (0.97) and TLI (0.96). Theoretical validity was assessed by correlating the results of the Polish version of the FIQ with the results of the Beck's Depression Inventory (BDI). Both the FIQ-Pol total score and its domains showed strong positive correlations with BDI. Conclusion: The Polish FIQ is a reliable and valid tool to measure the functional disability and health status of Polish people with FM. [ABSTRACT FROM AUTHOR]

Background: Even though a fair amount of studies focus on depression among college students, the effect of perceived parenting styles on the incidence of major depressive disorder (MDD) among representative freshmen in Chinese context is scarcely studied. The aim of this study is to investigate the effect of parenting styles on MDD in Chinese freshmen. Methods: A total of 9,928 Chinese freshmen were recruited in 2018. 6985 valid questionnaires were collected at one-year follow-up. Composite International Diagnostic Interview 3.0 (CIDI-3.0) was used for the diagnosis of MDD. Egna Minnen Beträffande Uppfostran (EMBU) questionnaire and Beck Depression Inventory-II (BDI-II) were used to assess parenting styles and baseline depressive symptoms, respectively. The associations between parenting styles and MDD incidence was analyzed with logistic regression. Results: The incidence of MDD in freshmen was 2.23% (95%CI: 1.91-2.60%). Maternal overprotection (OR = 1.03, 95%CI: 1.01–1.05) and disharmony relationship between parents (OR = 2.35, 95% CI: 1.42–3.89) increased the risk of new-onset MDD in freshmen, respectively. Mild depressive symptoms (OR = 2.06, 95%CI: 1.06–4.02), moderate (OR = 4.64, 95%CI: 2.55–8.44) and severe depressive symptoms (OR = 7.46, 95%CI: 2.71–20.52) at baseline increased the risk of new-onset MDD. Conclusions: Maternal overprotection, disharmony relationship between parents and baseline depressive symptoms are risk factors for new-onset MDD in Chinese freshmen. [ABSTRACT FROM AUTHOR]

Background: Patients with long-COVID often complain of continuous fatigue, myalgia, sleep problems, cognitive dysfunction, and post-exertional malaise. No data are available on EMG recording of evoked myopotentials (M-waves) or exercise-induced alterations in long-COVID patients, providing evidence of muscle membrane fatigue. Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) develops in more than half of patients after an infectious disease, particularly viral diseases. A large proportion (around 70%) of these patients have neuromuscular disorders with M-wave alterations during and after exercise. Our hypothesis was that M-wave alterations would be also found in long-COVID patients, in association with neuromuscular symptoms, similar to ME/CFS.Methods: This retrospective observational ColGEM (Covid LonG Encéphalomyelite Myalgique) study compared 59 patients with long-COVID and 55 ME/CFS patients with a history of severe infection who presented before the COVID pandemic. All of these patients underwent the same protocol consisting of a questionnaire focusing on neural and neuromuscular disorders and M-wave recording in the rectus femoris muscle before, during, and 10 min after a progressive cycling exercise. Maximal handgrip strength (MHGS) and maximal exercise power were also measured. The frequency of symptoms and magnitude of M-wave changes in the two groups were compared using non-parametric and parametric tests.Results: The frequency of fatigue, myalgia, sleep problems, cognitive dysfunction, and post-exertional malaise as well as the magnitude of exercise-induced M-wave alterations were the same in the two groups. By contrast, digestive problems were less present in long-COVID. M-wave alterations were greater in ME/CFS patients as in those with long-COVID when the highest muscle strength and highest exercise performance were measured.Conclusions: These high clinical and biological similarities between long-COVID and ME/CFS support the hypothesis that SARS-Cov-2 infection can cause ME/CFS symptoms. Trial registration Registered retrospectively. [ABSTRACT FROM AUTHOR]

Introduction: Major depressive disorder (MDD) is one of the most common mental disorders worldwide, estimated to affect 10–15% of the population per year. Treatment resistant depression (TRD) is estimated to affect a third of these patients who show difficulties in social and occupational function, decline of physical health, suicidal thoughts and increased health care utilization. We describe the prevalence of MDD, TRD and associated healthcare resource utilization in Maccabi Healthcare Services (MHS), a 2.5 million-member state-mandated health service in Israel. Methods: All MHS members with an MDD diagnosis were identified within the years 2017–2018 and prevalence assessed by age, sex and TRD. To assess the incidence of MDD, members aged 18–65 years at the start of any MDD episode were identified between 1st January 2016 and 31st May 2018 with at least one systemic first-line antidepressant treatment within three months before or after the initial episode. Treatment patterns, time on first-line treatment, and healthcare resource utilization were compared by TRD. Results: A total of 4960 eligible MDD patients were identified (median age = 51 years, 65% female), representing a period prevalence of 0.218%, and of those, a high proportion of patients received drug treatment (92%). Among incident MDD cases (n = 2553), 24.4% had TRD. Factors associated with TRD included increasing age and personality disorder. Median time on treatment was 3.7 months (longer for those without TRD than those with) and 81.9% of patients purchased more than one month's supply of therapy. In the year after index, patients with TRD had a significant increased number of visits to primary care physicians, psychiatrists, emergency room visits, general hospitalizations, and psychiatric hospitalizations. Conclusion: Our study shows that prevalence of MDD in Israel is low compared to other countries, however once diagnosed, patients' are likely to receive drug treatment. Among patients diagnosed with MDD, the proportion of TRD is similar to other countries, increases with age and is associated with increased healthcare utilization, therefore should be a focus of continued research for finding effective long term treatment options. [ABSTRACT FROM AUTHOR]

Background: Major depressive disorder (MDD) is a common recurrent mental disorder and one of the leading causes of disability in the world. The recurrence of MDD is associated with increased psychological and social burden, limitations for the patient, family, and society; therefore, action to reduce and prevent the recurrence of this disorder or hospital readmissions for depression among the patients is essential. Methods: The data of this retrospective cohort study were extracted from records of 1005 patients with MDD hospitalized in Farshchian hospital in Hamadan city, Iran (2011–2018). The hospital readmissions rate due to depression episodes was modeled using generalized Poisson regression (GPR). Demographic and clinical characteristics of the patients were considered as explanatory variables. SAS v9.4 was used (P < 0.05). Results: A majority of the patients were male (66.37%). The mean (standard deviation) of age at onset of MDD and the average number of hospital readmissions were 32.39 (13.03) years and 0.53 (1.84), respectively (most patients (74.3%) did not experience hospital readmissions). According to the results of the GPR, the lower age at the onset of the disease (IRR = 1.02;P = 0.008), illiteracy (IRR = 2.06;P = 0.003), living in urban areas (IRR = 1.56;P = 0.015), history of psychiatric illnesses in the family (IRR = 1.75;P = 0.004), history of emotional problems (IRR = 1.42;P = 0.028) and having medical disorders (IRR = 1.44;P = 0.035) were positively associated with the number of hospitalizations. Conclusion: According to our findings, urbanization, early onset of the disease, illiteracy, family history of mental illness, emotional problems, and medical disorders are among major risk factors associated with an increased number of hospital readmissions of MDD. [ABSTRACT FROM AUTHOR]

Background: Schizophrenia is a multifactorial disease involving interactions between genetic and environmental factors. Vitamin D has recently been linked to many metabolic diseases and schizophrenia. Vitamin D plays essential roles in the brain in the context of neuroplasticity, neurotransmitter biosynthesis, neuroprotection, and neurotransmission. Vitamin D receptors are demonstrated in most brain regions that are related to schizophrenia. However, very few studies in the literature examine the effects of 25-hydroxyvitamin D (25OHD) on schizophrenia symptoms. Methods: This study aimed to examine the effects of vitamin D replacement on positive, negative, and cognitive symptoms of schizophrenia. Serum 25OHD levels of 52 schizophrenia patients were measured. SANS and SAPS were used to evaluate the severity of schizophrenia symptoms, and the Wisconsin Card Sorting Test: CV4 was used for cognitive assessment. The study was completed with 40 patients for various reasons. The patients whose serum 25OHD reached optimal levels after vitamin D replacement were reevaluated with the same scales in terms of symptom severity. The SPSS 25 package program was used for statistical analysis. The Independent-Samples t-test was used to examine the relationship between the variables that may affect vitamin D levels and the vitamin D level and to examine whether vitamin D levels had an initial effect on the scale scores. Results: The mean plasma 25OHD levels of the patients was 17.87 ± 5.54. A statistically significant relationship was found only between the duration of sunlight exposure and 25 OHD level (p < 0.05). The mean SANS and SAPS scores of the participants after 25OHD replacement (23.60 ± 15.51 and 7.78 ± 8.84, respectively) were statistically significantly lower than mean SANS and SAPS scores before replacement (51.45 ± 17.96 and 18.58 ± 15.59, respectively) (p < 0.001 for all). Only the total attention score was significantly improved after replacement (p < 0.05). Conclusion: The data obtained from our study suggest that eliminating the 25OHD deficiency together with antipsychotic treatment can improve the total attention span and positive and negative symptoms in schizophrenia. The 25OHD levels should be regularly measured, replacement should be started when necessary, and the patients should be encouraged to get sunlight exposure to keep optimal 25OHD levels. [ABSTRACT FROM AUTHOR]

Juvenile primary fibromyalgia syndrome (JPFS) is a chronic musculoskeletal pain syndrome affecting children and adolescents. In part one of this review, we discussed the epidemiology, etiology, pathogenesis, clinical manifestations and diagnosis of JPFS. Part two focuses on the treatment and prognosis of JPFS. Early intervention is important. The standard of care is multidisciplinary, combining various modalities—most importantly, exercise and cognitive behavioral therapy. Prognosis varies and symptoms may persist into adulthood. [ABSTRACT FROM AUTHOR]

Background: Fibromyalgia (FM) is a generalized, widespread chronic pain disorder affecting 2.7% of the general population. In recent years, different studies have observed a strong association between FM and psychological trauma. Therefore, a trauma-focused psychotherapy, such as eye movement desensitization and reprocessing (EMDR), combined with a non-invasive brain stimulation technique, such as multifocal transcranial current stimulation (MtCS), could be an innovative adjunctive treatment option. This double-blind randomized controlled trial (RCT) analyzes if EMDR therapy is effective in the reduction of pain symptoms in FM patients and if its potential is boosted with the addition of MtCS. Methods: Forty-five patients with FM and a history of traumatic events will be randomly allocated to Waiting List, EMDR + active-MtCS, or EMDR + sham-MtCS. Therapists and patients will be kept blind to MtCS conditions, and raters will be kept blind to both EMDR and MtCS. All patients will be evaluated at baseline, post-treatment, and follow-up at 6 months after post-treatment. Evaluations will assess the following variables: sociodemographic data, pain, psychological trauma, sleep disturbance, anxiety and affective symptoms, and wellbeing. Discussion: This study will provide evidence of whether EMDR therapy is effective in reducing pain symptoms in FM patients, and whether the effect of EMDR can be enhanced by MtCS. Trial registration: ClinicalTrials.gov NCT04084795. Registered on 2 August 2019. [ABSTRACT FROM AUTHOR]

Systemic sclerosis (SSc) is a multi-organ autoimmune disease with complex interactions between immune-mediated inflammatory processes and vascular pathology leading to small vessel obliteration, promoting uncontrolled fibrosis of skin and internal organs. Interstitial lung disease (ILD) is a common but highly variable manifestation of SSc and is associated with high morbidity and mortality. Treatment approaches have focused on immunosuppressive therapies, which have shown some efficacy on lung function. Recently, a large phase 3 trial showed that treatment with nintedanib was associated with a reduction in lung function decline. None of the conducted randomized clinical trials have so far shown convincing efficacy on other outcome measures including quality of life determined by patient reported outcomes. Little evidence is available for non-pharmacological treatment and supportive care specifically for SSc-ILD patients, including pulmonary rehabilitation, supplemental oxygen, symptom relief and adequate information. Improved management of SSc-ILD patients based on a holistic approach is necessary to support patients in maintaining as much quality of life as possible throughout the disease course and to improve long-term outcomes. [ABSTRACT FROM AUTHOR]

Background: Treatment resistant depression (TRD) is common among patients with depression, and is associated with clinical and functional disability. However, the risk and risk factors for being granted disability pension (DP) among patients with TRD have not been investigated. Methods: All antidepressant initiators in Sweden with a diagnosis of depression in specialized care were identified in nationwide registers 2006–2013 and followed regarding treatment trials. TRD was defined as the start of a third sequential trial. Patients with TRD who were not on DP (N = 3204) were matched by age, sex, history of depression, calendar year, and time for treatment start with 3204 comparators with depression and ongoing antidepressant treatment. A proportional Cox Regression was performed with DP as outcome, adjusted for various sociodemographic and clinical covariates. Results: Compared to the comparison cohort, TRD was associated with a doubled risk for all-cause DP (aHR 2.07; 95%CI 1.83–2.35), DP due to depression (2.28; 1.82–2.85) and to any mental disorder (2.24; 1.95–2.57) but not due to somatic diagnoses (1.25; 0.84–1.86). Among significant risk factors for DP in TRD were female sex, being > 29 years of age, unemployment and a diagnosis of comorbid personality disorder (ICD-10 codes F60.0–9). Conclusion: TRD is associated with an elevated risk for DP compared to other patients with depression, with large potential costs for the affected patients and for society. Clinical and therapeutic implications for patients with TRD who are granted DP should be further investigated. Limitation: No clinical data, e.g. type of depression or reason for treatment switch, was available for this study. [ABSTRACT FROM AUTHOR]

Background: The incidence and burden of depressive disorders are increasing in South Korea. There are many differences between pharmaceutically treated depression (PTD) and treatment-resistant depression (TRD), including the economic consequences; however, to our knowledge, the economic burden of depression is understudied in South Korea. Therefore, the objective of the present study was to calculate the different economic costs of PTD and TRD in South Korea, specifically by comparing several aspects of medical care.Methods: This study comprised patients aged 18 and over who were newly prescribed antidepressants for more than 28 days with a depression code included from January 1, 2012, to December 31, 2012, by the Health Insurance Review and Assessment Service (HIRA). TRD was classified as more than two antidepressant regimen failures in PTD patients. The cost was calculated based on the cost reflected on the receipt registered with HIRA.Results: Of the 834,694 patients with PTD, 34,812 patients (4.17%) were converted to TRD. The cost of medical care for TRD (6,610,487 KRW, 5881 USD) was approximately 5 times higher than the cost of non-TRD (1,273,045 KRW, 1133 USD) and was significantly higher for patients with or without depression and suicide codes. Medical expenses incurred by non-psychiatrists were roughly 1.7 times higher than those incurred by psychiatrists.Conclusions: TRD patients had significantly higher healthcare costs than PTD patients. Identifying these financial aspects of care for depression can help to establish a more effective policy to reduce the burden on mentally ill patients. [ABSTRACT FROM AUTHOR]

Background: Although the individual and economic disease burden of depression is particularly high for long-term symptoms, little is known of the lifetime course of chronic depression. Most evidence derives from clinical samples, and the diagnostic distinction between persistent depressive disorder (PDD) and non-chronic major depression (NCMDD) is still debated. Thus, we examined characteristics of PDD among clinical vs. non-clinical cases, and the associated disease burden at a population level. Methods: Data were drawn from the mental health module of the German Health Interview and Examination Survey for Adults (DEGS1-MH, 2009–2012, n = 4483) and a clinical sample of PDD inpatients at Charité – Universitätsmedizin Berlin (2018–2019, n = 45). The DSM-5 definition of PDD was operationalized a priori to the study using interview-based DSM-IV diagnoses of dysthymia and major depression lasting at least 2 years in both surveys. Additional depression characteristics (depression onset, self-classified course, suicidality, comorbid mental disorders, treatment history and current depressive symptoms [Patient Health Questionnaire-9]) were assessed. In the DEGS1-MH, health-related quality of life (Short Form Health Survey-36, SF-36), chronic somatic conditions, number of sick days (past 12 months) or days with limitations in normal daily life activities (past 4 weeks), and health service utilization (past 12 months) were compared for PDD vs. NCMDD. Results: PDD cases from the clinical sample had a significantly earlier depression onset, a higher proportion of self-classification as persistent course, and treatment resistance than PDD and NCMDD cases in DEGS1-MH. At a population level, PDD cases showed worse outcomes compared with NCMDD cases in terms of somatic comorbidity, SF-36 mental component score, and activity limitations owing to mental health problems, as well as a higher risk for outpatient mental health care contact. Conclusions: The distinction between PDD and NCMDD proposed for DSM-5 seems warranted. Early onset depression, self-classification as persistent depressive course, and treatment resistance are suggested as markers of more severe and chronic depression courses. At a population level, PDD is associated with remarkably higher individual and economic disease burden than NCMDD, highlighting the need to improve medical recognition of chronic courses and establish specific treatment concepts for chronic depression. [ABSTRACT FROM AUTHOR]

Background: In the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, a third of patients did not achieve remission or adequate response after two treatment trials, fulfilling requirements for treatment resistant depression (TRD). The present study is a secondary analysis of the STAR*D data conducted to compare the humanistic outcomes in patients with TRD and non-TRD MDD. Methods: Patients with major depressive disorder who entered level 3 of the STAR*D were included in the TRD group, while patients who responded to treatment and entered follow-up from level 1 or 2 were included in the non-TRD group. The first visit in level 1 was used for baseline assessments. The time-point of assessments for comparison was the first visit in level 3 for TRD patients (median day: 141), and the visit closest to 141 ± 60 days from baseline for non-TRD patients. Outcomes were assessed by the 12-item Short Form Health Survey (SF12), 16-item Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), Work and Social Adjustment Scale (WSAS), and Work Productivity and Activity Impairment scale (WPAI). Scores were compared in a linear model with adjustment for covariates including age, gender, and depression severity measured by the 17-item Hamilton Rating Scale for Depression (HDRS17) and Quick Inventory of Depressive Symptomatology (QIDS). Results: A total of 2467 (TRD: 377; non-TRD: 2090) patients were studied. TRD patients were slightly older (mean age 44 vs 42 years), had a higher proportion of men (49% vs 37%, p < .0001), and baseline depression severity (HDRS17: 24.4 vs 22.0, p < .0001) vs non-TRD patients. During follow-up, TRD patients had lower health-related quality of life (HRQOL) scores on mental (30 vs 45.7) and physical components (47.7 vs 48.9) of the SF12, and lower Q-LES-Q scores (43.6 vs 63.7), greater functional and work impairments and productivity loss vs non-TRD patients (all p < 0.05). Conclusion: Patients with TRD had worse HRQOL, work productivity, and social functioning than the non-TRD patients. [ABSTRACT FROM AUTHOR]

Background: Several psychological sequelae have been identified in civilian war survivors. However, little is known about the prevalence of obsessive-compulsive symptoms and their relationship to trauma in this population. Method: Fifty-one adult civilian survivors of the Kosovo War (28 males) who had immigrated to Switzerland completed the Revised Obsessive-Compulsive Inventory Scale, the Posttraumatic Stress Diagnostic Scale and the Hopkins Symptom Checklist. Data were analysed using multiple regression analyses. Results: Overall, 35 and 39 % of the sample scored above the cut-offs for likely obsessive-compulsive disorder and posttraumatic stress disorder, respectively. Participants with high levels of posttraumatic stress symptoms were significantly more likely to have obsessive-compulsive symptoms, and vice versa. In multiple regression analysis, gender and severity of posttraumatic stress symptoms were predictors of obsessive-compulsive symptoms, whereas number of traumatic life event types and depressive symptoms were not. Conclusion: Given the small sample size, the results of this study need to be interpreted cautiously. Nevertheless, a surprisingly high number of participants in our study suffered from both obsessive-compulsive and posttraumatic stress symptoms, with obsessive-compulsive symptoms tending to be more pronounced in women. It remains, therefore, critical to specifically assess both obsessive-compulsive and posttraumatic stress symptoms in civilian war survivors, and to provide persons afflicted with appropriate mental health care. [ABSTRACT FROM AUTHOR]

Background: Suboptimal vitamin D levels have been identified in populations with psychotic disorders. We sought to explore the relationship between vitamin D deficiency, clinical characteristics and cardiovascular disease risk factors among people with established psychosis. Methods: Vitamin D levels were measured in 324 community dwelling individuals in England with established psychotic disorders, along with measures of mental health, cardiovascular risk and lifestyle choices. Vitamin D deficiency was defined as serum 25-hydroxyvitamin D (25-OHD) levels below 10 ng/ml (equivalent to <25 nmol/L) and "sufficient" Vitamin D as above 30 ng/ml (>50 nmol/L). Results: The mean 25-OHD serum level was 12.4 (SD 7.3) ng/ml, (range 4.0-51.7 ng/ml). Forty nine percent (n = 158) were vitamin D deficient, with only 14% (n = 45) meeting criteria for sufficiency. Accounting for age, gender, ethnicity and season of sampling, serum 25-OHD levels were negatively correlated with waist circumference (r = -0.220, p < 0.002), triglycerides (r = -0.160, p = 0.024), total cholesterol (r = -0.144, p = 0.043), fasting glucose (r = -0.191, p = 0.007), HbA1c (r = -0.183, p = 0.01), and serum CRP levels (r = -0.211, p = 0.003) and were linked to the presence of metabolic syndrome. Conclusions: This is the largest cross sectional study of serum 25-OHD levels in community dwelling individuals with established psychosis, indicating a high level of vitamin D deficiency. Lower vitamin D levels are associated with increased cardiovascular disease risk factors and in particular metabolic syndrome. Further research is needed to define appropriate protocols for vitamin D testing and supplementation in practice to see if this can improve cardiovascular disease risk. [ABSTRACT FROM AUTHOR]

Background: Anxiety and related disorders are among the most common mental disorders, with lifetime prevalence reportedly as high as 31%. Unfortunately, anxiety disorders are under-diagnosed and under-treated. Methods: These guidelines were developed by Canadian experts in anxiety and related disorders through a consensus process. Data on the epidemiology, diagnosis, and treatment (psychological and pharmacological) were obtained through MEDLINE, PsycINFO, and manual searches (1980-2012). Treatment strategies were rated on strength of evidence, and a clinical recommendation for each intervention was made, based on global impression of efficacy, effectiveness, and side effects, using a modified version of the periodic health examination guidelines. Results: These guidelines are presented in 10 sections, including an introduction, principles of diagnosis and management, six sections (Sections 3 through 8) on the specific anxiety-related disorders (panic disorder, agoraphobia, specific phobia, social anxiety disorder, generalized anxiety disorder, obsessive-compulsive disorder, and posttraumatic stress disorder), and two additional sections on special populations (children/adolescents, pregnant/lactating women, and the elderly) and clinical issues in patients with comorbid conditions. Conclusions: Anxiety and related disorders are very common in clinical practice, and frequently comorbid with other psychiatric and medical conditions. Optimal management requires a good understanding of the efficacy and side effect profiles of pharmacological and psychological treatments. [ABSTRACT FROM AUTHOR]

Background Previous studies have found an association between psychiatric disorders and vitamin D deficiency, but most studies have focused on depression. This study aimed to establish the prevalence of vitamin D deficiency in elderly patients with a wider range of psychiatric diagnoses. Method The study included elderly patients (>64 years) referred to a psychiatric hospital in Northern Norway and a control group from a population survey in the same area. An assessment of psychiatric and cognitive symptoms and diagnoses was conducted using the Montgomery and Aasberg Depression Rating Scale, the Cornell Scale for Depression in Dementia, the Mini Mental State Examination, the Clockdrawing Test, and the Mini International Neuropsychiatric Interview (MINI+), as well as clinical interviews and a review of medical records. The patients' mean level of 25-hydroxyvitamin D (25(OH)D) and the prevalence of vitamin D deficiency were compared with those of a control group, and a comparison of vitamin D deficiency across different diagnostic groups was also made. Vitamin D deficiency was defined as 25(OH)D <50 nmol/L (<20 ng/ml). Results The mean levels of 25(OH)D in the patient group (n = 95) and the control group (n = 104) were 40.5 nmol/L and 65.9 nmol/L (p < 0.001), respectively. A high prevalence of vitamin D deficiency was found in the patient group compared with the control group (71.6% and 20.0%, respectively; p < 0.001). After adjusting for age, gender, season, body mass index, and smoking, vitamin D deficiency was still associated with patient status (OR: 12.95, CI (95%): 6.03-27.83, p < 0.001). No significant differences in the prevalence of vitamin D deficiency were found between patients with different categories of psychiatric diagnoses, such as depression, bipolar disorders, psychosis, and dementia. Conclusion Vitamin D deficiency is very common among psychogeriatric patients, independent of diagnostic category. Even though the role of vitamin D in psychiatric disorders is still not clear, we suggest screening for vitamin D deficiency in this patient group due to the importance of vitamin D for overall health. [ABSTRACT FROM AUTHOR]

Background: Bipolar disorder (BD) is a psychiatric illness defined by pathological alterations between the mood states of mania and depression, causing disability, imposing healthcare costs and elevating the risk of suicide. Although effective treatments for BD exist, variability in outcomes leads to a large number of treatment failures, typically followed by a trial and error process of medication switches that can take years. Pharmacogenetic testing (PGT), by tailoring drug choice to an individual, may personalize and expedite treatment so as to identify more rapidly medications well suited to individual BD patients. Discussion: A number of associations have been made in BD between medication response phenotypes and specific genetic markers. However, to date clinical adoption of PGT has been limited, often citing questions that must be answered before it can be widely utilized. These include: What are the requirements of supporting evidence? How large is a clinically relevant effect? What degree of specificity and sensitivity are required? Does a given marker influence decision making and have clinical utility? In many cases, the answers to these questions remain unknown, and ultimately, the question of whether PGT is valid and useful must be determined empirically. Towards this aim, we have reviewed the literature and selected drug-genotype associations with the strongest evidence for utility in BD. Summary: Based upon these findings, we propose a preliminary panel for use in PGT, and a method by which the results of a PGT panel can be integrated for clinical interpretation. Finally, we argue that based on the sufficiency of accumulated evidence, PGT implementation studies are now warranted. We propose and discuss the design for a randomized clinical trial to test the use of PGT in the treatment of BD. [ABSTRACT FROM AUTHOR]

It is of importance whether myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a variant of sickness behavior. The latter is induced by acute infections/injury being principally mediated through proinflammatory cytokines. Sickness is a beneficial behavioral response that serves to enhance recovery, conserves energy and plays a role in the resolution of inflammation. There are behavioral/ symptomatic similarities (for example, fatigue, malaise, hyperalgesia) and dissimilarities (gastrointestinal symptoms, anorexia and weight loss) between sickness and ME/CFS. While sickness is an adaptive response induced by proinflammatory cytokines, ME/ CFS is a chronic, disabling disorder, where the pathophysiology is related to activation of immunoinflammatory and oxidative pathways and autoimmune responses. While sickness behavior is a state of energy conservation, which plays a role in combating pathogens, ME/CFS is a chronic disease underpinned by a state of energy depletion. While sickness is an acute response to infection/injury, the trigger factors in ME/CFS are less well defined and encompass acute and chronic infections, as well as inflammatory or autoimmune diseases. It is concluded that sickness behavior and ME/CFS are two different conditions. [ABSTRACT FROM AUTHOR]

Background: White matter abnormalities can cause network dysfunction that underlies major depressive disorder (MDD). Diffusion tensor imaging (DTI) is used to examine the neural connectivity and integrity of the white matter. Previous studies have implicated frontolimbic neural networks in the pathophysiology of MDD. Approximately 30% of MDD patients demonstrate treatment-resistant depression (TRD). However, the neurobiology of TRD remains unclear. Methods: We used a voxel-based analysis method to analyze DTI data in young patients with TRD (n = 30; 19 males, 11 females) compared with right-handed, age- and sex-matched healthy volunteers (n = 25; 14 males, 11 females). Results: We found a significant decrease in fractional anisotropy (FA) (corrected, cluster size >50) in the left middle frontal gyrus (peak coordinates [-18 46-14]), left limbic lobe uncus (peak coordinates [-18 2-22]), and right cerebellum posterior lobe (peak coordinates [26-34 -40]). There was no increase in FA in any brain region in patients. We also found a significant negative correlation between mean regional FA values in the three areas and Beck Depression Inventory symptom scores. Conclusions: We found significant differences in white matter FA in the frontal lobe, limbic lobe and cerebellum between TRD patients and controls. These data suggest that abnormalities of cortical-limbic-cerebellar white matter networks may contribute to TRD in young patients. [ABSTRACT FROM AUTHOR]

Background Sense of Coherence (SOC) is a measure of an individual's capacity to use various coping mechanisms and resources when faced with a stressor. Chronic pain is one of the most prevalent and disabling conditions in clinical practice. This study examines the extent to which a strong SOC is associated with less pain and better health related quality of life (HRQoL) among patients with chronic pain. Methods We analyzed data from the Stepped Care to Optimize Pain care Effectiveness (SCOPE) trial which enrolled 250 patients with persistent (3 months or longer) musculoskeletal pain who were receiving care in an United States Department of Veterans Affairs (VA) primary care clinic. The abbreviated three-item SOC scale was used to measure personal coping capability. Participants were categorized into Strong SOC (score 0-1) and Weak SOC (score 2-6). The Brief Pain Inventory (BPI) was used to assess the severity and disability associated with pain. Additionally, pain self-efficacy (ASES) and catastrophizing (CSQ) were assessed. HRQoL was assessed with the 36-item Short-Form Health Survey (SF-36) social functioning, vitality, and general health subscales. Multiple linear regression models were performed to examine whether SOC was independently associated with pain-specific and HRQoL outcomes, after adjusting for sociodemographic and socioeconomic characteristics, medical comorbidities and major depression. Results Of the 250 study patients, 61% had a strong SOC whereas 39% had a weak SOC. Multivariable linear regression analysis showed that a strong SOC was significantly associated with better general health, vitality, social functioning and pain self-efficacy as well as less pain catastrophizing. These significant findings were partially attenuated, but remained statistically significant, after controlling for major depression. SOC was not significantly associated with pain severity or pain disability. Conclusions A strong SOC is associated with better HRQoL and self-efficacy as well as less catastrophizing in patients with chronic pain. SOC may be an important coping mechanism (strategy) for patients with chronic musculoskeletal pain. Trial registration clinicaltrials.gov Identifier: NCT00926588. [ABSTRACT FROM AUTHOR]

Background: Pain conditions of the musculoskeletal system are very common and have tremendous socioeconomic impact. Despite its high prevalence, musculoskeletal pain remains poorly understood and predominantly non-specifically and insufficiently treated. The group of chronic musculoskeletal pain patients is supposed to be heterogeneous, due to a multitude of mechanisms involved in chronic pain. Psychological variables, psychophysiological processes, and neuroendocrine alterations are expected to be involved. Thus far, studies on musculoskeletal pain have predominantly focused on the general aspects of pain processing, thus neglecting the heterogeneity of patients with musculoskeletal pain. Consequently, there is a need for studies that comprise a multitude of mechanisms that are potentially involved in the chronicity and spread of pain. This need might foster research and facilitate a better pathophysiological understanding of the condition, thereby promoting the development of specific mechanism-based treatments for chronic pain. Therefore, the objectives of this study are as follows: 1) identify and describe subgroups of patients with musculoskeletal pain with regard to clinical manifestations (including mental co-morbidity) and 2) investigate whether distinct sensory profiles or 3) distinct plasma levels of pain-related parameters due to different underlying mechanisms can be distinguished in various subgroups of pain patients. Methods/Design: We will examine a population-based chronic pain sample (n = 100), a clinical tertiary care sample (n = 100) and pain-free patients with depression or post-traumatic stress disorder and pain-free healthy controls (each n = 30, respectively). The samples will be pain localisation matched by sex and age to the population-based sample. Patients will undergo physical examination and thorough assessments of mental co-morbidity (including psychological trauma), perceptual and central sensitisation (quantitative sensory testing), descending inhibition (conditioned pain modulation, the diffuse noxious inhibitory control-like effect), as well as measurement of the plasma levels of nerve growth factor and endocannabinoids. Discussion: The identification of the underlying pathophysiologic mechanisms in different subgroups of chronic musculoskeletal pain patients will contribute to a mechanism-based subgroup classification. This will foster the development of mechanism-based treatments and holds promise to treat patients more sufficient. [ABSTRACT FROM AUTHOR]

Chronic fatigue syndrome is characterised by intense fatigue, with duration of over six months and associated to other related symptoms. The latter include asthenia and easily induced tiredness that is not recovered after a night's sleep. The fatigue becomes so severe that it forces a 50% reduction in daily activities. Given its unknown aetiology, different hypotheses have been considered to explain the origin of the condition (from immunological disorders to the presence of posttraumatic oxidative stress), although there are no conclusive diagnostic tests. Diagnosis is established through the exclusion of other diseases causing fatigue. This syndrome is rare in childhood and adolescence, although the fatigue symptom per se is quite common in paediatric patients. Currently, no curative treatment exists for patients with chronic fatigue syndrome. The therapeutic approach to this syndrome requires a combination of different therapeutic modalities. The specific characteristics of the symptomatology of patients with chronic fatigue require a rapid adaptation of the educational, healthcare and social systems to prevent the problems derived from current systems. Such patients require multidisciplinary management due to the multiple and different issues affecting them. This document was realized by one of the Interdisciplinary Work Groups from the Institute for Rare Diseases, and its aim is to point out the main social and care needs for people affected with Chronic Fatigue Syndrome. For this, it includes not only the view of representatives for different scientific societies, but also the patient associations view, because they know the true history of their social and sanitary needs. In an interdisciplinary approach, this work also reviews the principal scientific, medical, socio-sanitary and psychological aspects of Chronic Fatigue Syndrome. [ABSTRACT FROM AUTHOR]

Background: Depression is a significant health and economic burden worldwide affecting not only adults but also children and adolescents. Current treatment options for this group are scarce and show moderate effect sizes. There is emerging evidence that dietary patterns and specific nutritional components might play a role in the risk for developing depression. This study protocol focusses on the role of vitamin D which is for long known to be relevant for calcium and phosphorous homeostasis and bone health but might also impact on mental health. However, the assessment of the vitamin D status of depressed juvenile patients, or supplementation of vitamin D is currently not part of routine treatment. Controlled intervention studies are indispensable to prove whether a vitamin D deficiency ameliorates depressive symptoms. Methods/design: This double blinded, randomized controlled trial will enroll 200 inpatients from a child and adolescent psychiatric department with a vitamin D deficiency defined by a 25(OH)-vitamin D-level < 30 nmol/l (12 ng/ml) and a Beck Depressions Inventory (BDI-II) score > 13 (indicating at least: mild depression). Upon referral, all patients will be screened, checked for inclusion criteria, and those eligible will be randomized after written consent into a supplementation or placebo group. Both study-arms will receive treatment-as-usual for their psychiatric disorder according to established clinical guidelines. The participants of the vitamin D supplementation group will receive 2640 I.E. vitamin D3 q.d. for 28 days in accordance with best practice in pediatric endocrinology. We hypothesize that delaying supplementation of vitamin D in the placebo arm will affect the treatment success of the depressive symptomatology in comparison to the vitamin D supplementation group. Patients will be enrolled for a period of 28 days based on the mean length of hospitalization of juveniles with depression. Discussion: Randomized controlled trials in children and adolescents with depression are needed to elucidate the role of a vitamin D deficiency for mental disorders and to investigate the relevance of a routine assessment and supplementation of vitamin D deficits. Trial registration: DRKS00009758, 16/06/2016 (retrospectively registered). [ABSTRACT FROM AUTHOR]